Cerebellar Involvement in Alcohol Use Disorder (AUD)

NCT05732207 | Recruiting

• 2 other identifiers: IRB00337209R01AA030368
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational and interventional study is to better understand the involvement of the cerebellum in the brain reward system in persons with alcohol use disorder (AUD). The main questions it aims to answer are:

1. 1.What is the nature of cerebellar input to the ventral tegmental area (VTA) in the brain reward system, and how is it perturbed in AUD?
2. 2.What is the relationship between measures of cerebellar integrity and magnitude of reward activation to alcohol-related cues in cerebellar, VTA and other brain reward structures?
3. 3.What is the therapeutic potential of cerebellar transcranial direct current stimulation (tDCS) for modulating alcohol cue reactivity, associated alcohol craving, and cerebellar - VTA functional connectivity in the brain reward system? Persons with AUD will be compared with healthy control participants.

Conditions

Alcohol Use Disorder

Keywords

AUD; heavy drinking; hazardous drinking

Outcome Measures

Primary Outcomes (10)

• Craving for alcohol during the cue reactivity task as assessed by a rating scale

  Participants will view blocks of pictures of alcohol and non-alcohol beverages, as well as control pictures and periods of rest. Participant rating of alcohol craving are obtained during the picture presentations using one of 5 buttons placed under their fingers, where 5 (thumb) = Extreme, 4=Severe, 3=Moderate, 2=Mild, 1=None

  28 minutes

• Resting state functional connectivity during tDCS

  Participants will rest quietly during tDCS administration

  28 minutes

• Brain activation to alcohol cues

  Participants will view blocks of pictures of alcohol and non-alcohol beverages, as well as control pictures and periods of rest. Brain activation will be measured from the fMRI signal on alcohol minus non-alcohol conditions.

  28 minutes

• Brain functional connectivity to alcohol vs non-alcohol cues

  A psychophysiological interaction (PPI) analysis will be used to determine if brain connectivity between the cerebellum and reward areas changes when viewing alcohol versus non-alcohol pictures

  28 minutes

• Brain activation related to reward prediction during the monetary incentive task

  The monetary incentive task is performed during fMRI scanning. Two different cue symbols (dollar sign vs circle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Brain activation during reward prediction will be measured by the post-cue activation on dollar sign versus circle trials.

  18 minutes

• Brain functional connectivity related to reward prediction during the monetary incentive task

  The monetary incentive task is performed during fMRI scanning. Two different cue symbols (dollar sign vs circle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Functional connectivity between the cerebellum and reward structures during reward prediction will be measured by a PPI analysis that measures post-cue functional connectivity on dollar sign versus circle trials.

  18 minutes

• Brain activation to reward prediction error during the monetary incentive task

  Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Brain activation to reward prediction error will be measured from the activation observed after the participant receives feedback on his/her winnings, by contrasting trials in which reward obtained is equal to the amount expected versus not equal to the amount expected.

  18 minutes

• brain functional connectivity to reward prediction error during the monetary incentive task

  Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Functional connectivity between the cerebellum and reward structures to reward prediction error will be measured using a PPI on the connectivity that is observed after the participant receives feedback on his/her winnings, by contrasting trials in which reward obtained is equal to the amount expected versus not equal to the amount expected.

  18 minutes

• Percentage of trials with a conditioned response during the classical eyeblink conditional task

  Eyeblink conditioning involves pairing a neutral stimulus, e.g. an auditory conditioned stimulus (CS), with an air puff to the eye region. This unconditioned stimulus (US) evokes an unconditioned response (UR) that is detected by measuring the eyeblink. After repeated pairings of the CS and US, participants learn to blink in response to the conditioned stimulus and before air puff onset. The CS-US pairing dependent eyeblink that anticipates the onset of the US is referred to as the conditioned response (CR).

  21 minutes

• Mean time (in milliseconds) at which peak of conditioned response occurs during the classical eyeblink conditional task

  Eyeblink conditioning involves pairing a neutral stimulus, e.g. an auditory conditioned stimulus (CS), with an air puff to the eye region. This unconditioned stimulus (US) evokes an unconditioned response (UR) that is detected by measuring the eyeblink. After repeated pairings of the CS and US, participants learn to blink in response to the conditioned stimulus and before air puff onset. The CS-US pairing dependent eyeblink that anticipates the onset of the US is referred to as the conditioned response (CR).

  21 minutes

Secondary Outcomes (2)

• Baseline cerebral blood flow (CBF) measured from a CBF MRI scan

  4 minutes and 40 seconds

• Behavioral accuracy during the monetary incentive task

  18 minutes

Study Arms (3)

Cathodal cerebellar transcranial direct current stimulation (ctDCS)

EXPERIMENTAL

For ctDCS, the cathodal (-) electrode will be positioned over the right cerebellum 1 cm below and 3 cm lateral to the inion, and the anodal (+) electrode will be placed on the contralateral supraorbital area (FP2 EEG location).

Procedure: cerebellar transcranial direct current stimulation

Anodal cerebellar transcranial direct current stimulation (atDCS)

EXPERIMENTAL

For atDCS, anode/cathode locations are reversed from those of ctDCS..

Procedure: cerebellar transcranial direct current stimulation

Sham cerebellar transcranial direct current stimulation (stDCS)

SHAM COMPARATOR

For stDCS, the electrodes will be configured randomly as atDCS 50% of the time, and as ctDCS 50% of the time.

Procedure: cerebellar transcranial direct current stimulation

Interventions

cerebellar transcranial direct current stimulation PROCEDURE

TDCS is a safe and non-invasive technique for modulating cortical excitability and behavior. TDCS, delivered via surface electrodes, induces an intracerebral current flow sufficient to achieve changes in cortical excitability. Anodal stimulation up-regulates cortical excitability, while cathodal stimulation decreases excitability.

Anodal cerebellar transcranial direct current stimulation (atDCS); Cathodal cerebellar transcranial direct current stimulation (ctDCS); Sham cerebellar transcranial direct current stimulation (stDCS)

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• completed at least 8 years of education

You may not qualify if:

• Estimated Intelligence Quotient (IQ) \< 90
• less than 5th grade reading level
• Left handed
• Non-fluent in English
• current drug use disorder other than alcohol (except nicotine and caffeine) and or recent drug use in the last 90 days
• Positive breath alcohol level at time of MRI scan or discrepancies between alcohol biomarker and self-report that cannot be resolved
• Exhibiting symptoms of alcohol withdrawal on visit 1 assessment
• Significant current psychiatric distress and or treatment
• History of any central nervous system disorder, presence of a seizure disorder, or use of anticonvulsant medication in the past 3 months
• any serious medical condition detected on assessment or by medical record review; or have liver function tests more than three times normal at screening
• History of metal implantation that would preclude MRI scanning; or other implants, pumps, pacemakers that would be contraindications for MRI scanning
• Abnormal MRI scan or history of significant closed head trauma
• Evidence of dementia
• For women, pregnancy

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

RECRUITING

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• John E Desmond, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John E Desmond, PhD

CONTACT

410-502-3583; jdesmon2@jhmi.edu

JoAnna Mathena

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Electrode location and duration of stimulation will be masked
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: AUD and age- and gender matched control participants will be tested under sham, cathodal, and anodal tDCS (in counterbalanced order)

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: February 16, 2023
• Study Start: October 12, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

US (1)